Genetic Mutation Assessment of NPM1 Gene and Gene Expression of MDR1 in Iraqi Patients with Acute Myeloid Leukemia

Abstract

Since its discovery, mutations in NPM1 have been frequently associated with a large number of Acute Myeloid Leukemia (AML) patients. The vast majority of genetic changes were previously detected in exon 12, however little information report mutations in Nuclear Export Signal region (NES) of NPM1. Sequencing analysis included exon 2 and 3 for 75 Iraqi AML patients showed three SNPs, G/A792, G/A794 and G/A797 were detected within intron region of 90% AML and 70% healthy subjects. Other SNPs were only detected in AML subjects in which single nucleotide variant was identified in exon 3 of 70% AML subjects (A/G1275 rs753788683) in addition, two SNPs (G/A635 and G/A660) within intron region of 80% of AML subjects were detected. No genetic variation observed inexon 2 of amplified NPM1 gene. The correlation between MDR1 gene over expression and resistance to chemotherapy treatment showed no significant differences in gene expression between newly diagnosed and first-course induction subjects. Nevertheless, significant decreases in CT value were recorded for both the second induction AML and AML consolidation patients with p value of 0.0258 and 0.0007, respectively, as compared with healthy controls, indicating the induction of higher expression of MDR1 gene by increasing the challenge of AML patients with chemotherapy regimen.